magbiovin projectffhglasnik.ffh.bg.ac.rs/wp-content/uploads/2019/03/konferencija-_finalfinal.pdf ·...
TRANSCRIPT
“Vinca” Institute of Nuclear Sciences
MAGBIOVIN project
Conference: "Magnetic nanoparticles and their applications in medicine"
Date: April 4-5, 2019.
Venue: Rectorate of the University of Belgrade, Studentski Trg 1, Belgrade
Conference organizer: Project MAGBIOVIN, “Vinca” Institute of Nuclear
Sciences
Conference organizing committee
Bratislav Antic, Magbiovin project coordinator
ZeljkoPrijovic, Era Chair Magbiovin project
Vojislav Spasojevic
Vladan Kusigerski
Jovan Blanusa
Marija Perovic
Ana Mrakovic
Marko Boskovic
Milos Ognjanovic
Luka Ivancic
Maria del Puerto Morales
Gerardo F. Goya
SanjaVranjes-Djuric
Drina Jankovic
Magdalena Radovic
Marija Mirkovic
Aleksandar Vukadinovic
Dalibor Stankovic
Zorana Milanovic
Project MAGBIOVIN
The MAGBIOVIN project is focused on the development of novel magnetic nanomaterials
designed for biomedical applications, as a basis for new tumor therapies. Their antitumor effect
is based on the ability of nanoparticles to spontaneously accumulate or to be driven into tumor by
the magnets, and when exposed to an oscillatory magnetic field they release heat (magnetic
hyperthermia). With the addition of certain radionuclides that destroy the tumor by radiation or
drugs that are targeted releasing into tumor by the magnetic field, an increased localized
antitumor effect that saves healthy tissue is obtained. To this goal, the human tumor cell lines are
being investigated, and within the Center of Excellence, the "Vinca" Institute has formed a mice
vivarium without immune systems on which human tumors are grown, as the best testing model
for the effectiveness of new methods.
The MAGBIOVIN project is funded by the European Commission within the framework of the
FP7-EraChair Call-2013, and it is implemented in the 2014-2019 period.
Conference Scope
In the last decade the synergistic research between nanotechnology, materials science and
medicine demonstrated the great potential of interdisciplinary science. We have witnessed
important advances in what is now known as Nanomedicine, comprising many non-invasive,
highly specific diagnostics tools and therapies. The programme of the "Magnetic nanoparticles
and their applications in medicine" conference comprises sessions from several application
domains of nanotechnology, and it focuses on innovations in materials and their clinical
applications. To meet the challenges of a fast-evolving field as Nanomedicine, we have gathered
prominent scientists with most active contributions to their respective fields, which we are sure,
will result in a remarkable opportunity for the audience to get a first-hand overview of the latest
developments in nanomaterials and nanomedicine.
It is the wish of the Organizing Committee that the meeting also provide an excellent opportunity
to foster existing collaborations and to establish new contacts among our colleagues.
We wish the MAGBIOVIN Conference much success. May all participants enjoy this exchange
of ideas and have a vivid and exciting time at the conference.
Conference program
Thursday, 4th
April
09:30-09:45 Conference Opening
09:45-10:25 Quentin A. Pankhurst, “Biomedical Applications of Radionuclide-
Labelled Magnetic Nanoparticles”
10:25-11:05 Robert Ivkov, “The tumor immune microenvironment is reshaped
after systemic exposure to magnetic iron oxide nanoparticles: A study in mouse
models of breast cancer”
11:05-11:40 Coffee break
11:40-12:10 Florence Gazeau, “Long term fate of iron oxide nanoparticles in the
body: a long and comprehensive survey”
12:10-13:00 Adriele Prina-Mello, “Translational requirements for nanotechnology
enable medical products”
13:00-15:00 Lunch
15:00-15:40 Holger Grüll, “Nanoparticles for Molecular Imaging and Therapy”
15:40-16:20 Olivier Sandre, “Monocore or multicore iron oxide nanoparticles
synthesized in polyols and coated with a thermosensitive cell-penetrating peptide”
16:20-16:40 Coffee break
16:40-17:20 Željko Prijović, “Magnetic nanomaterial as a mediator, carrier and
trigger for hyperthermia-complementing combined therapies of tumors:
MagBioVin approach”
17:20-18:00 María del Puerto Morales,“Magnetic nanoparticles aggregation
effects on cellular magnetic hyperthermia”
Friday, 5th
April
09:45-10:25 Sanjay Mathur, “Chemically Engineered Iron Oxide Nanocrystals for
Transport of Biomolecules Across Biological Barriers”
10:25-11:05 Vittoria Raffa, “Mecanotransduction of axonal growth: a new
strategy based on magnetic nanoparticle to remote nerve regeneration”
11:05-11:40 Coffee break
11:40-12:10 Boris Polyak, “Nanomagnetic approaches for vascular healing and
cardiac regeneration”
12:10-13:00 Ana Espinosa, “Thermal therapies mediated by iron oxide-based
nanoparticles: quantitative comparison of heat generation, therapeutic efficiency
and limitations”
13:00-15:00 Lunch
15:00-15:40 Gerardo F. Goya, “On the feasibility of improving heat production in
magnetic fluid hyperthermia: the time of topology”
15:40-16:20 Giuseppe Cirillo, “Graphene oxide functional nanohybrids with
magnetic nanoparticles for improved vectorization of anticancer therapeutics”
16:20-16:40 Coffee break
16:40-17:20 Victor Kuncser,“Engineering and optimization of Specific Absorption
Rates of Fe oxide nanoparticles in magnetic hyperthermia”
17:20-18:00 David Serantes, “Taking magnetic hyperthermia and magnetogenetics
to the next level: key aspects to address from a basic-physics point of view”
18:00 Conference Closing
ABSTRACTS
Biomedical Applications of Radionuclide-Labelled Magnetic Nanoparticles
Quentin A. Pankhurst
Healthcare Biomagnetics Laboratory, University College London, London W1S 4BS
‘Healthcare Biomagnetics’ – the sensing, moving and heating of magnetic nanoparticles in vitro
or in the human body – offers the potential for safe and convenient alternatives for many
therapeutic and diagnostic applications. This is leading to the development of products such as
remote sensors, mechanical actuators, and therapeutic heat sources. In this lecture a selection of
recent examples of this work will be presented and discussed, with a particular focus on
applications involving the use of radionuclide-labelled magnetic nanoparticles.
Quentin Pankhurst
Professor Quentin Pankhurst is a Professor of Physics and
Director of the Healthcare Biomagnetics Laboratory at University
College London – one of the top universities in the UK, and
consistently rated one of the top 20 higher education institutions
in the world. Previously, in 2008, he was the Director of the
Davy-Faraday Research Laboratory at the Royal Institution of
Great Britain (in Mayfair, London), where he held a position once
held by such luminaries as Michael Faraday and Ernest
Rutherford. On his return to UCL in 2011, he set up the UCL
Institute of Biomedical Engineering, a cross-faculty institute that
brought together 250 PIs and their teams – more than a thousand researchers in total – in
common programmes based on translational research and experimental medicine.
Quentin’s work in bio- and nanomagnetism is directed towards making practical advances in the
use of magnetic nanoparticles in healthcare. In his career to date he has published more than 250
papers that have been cited more than 13,500 times, and he has generated more than £45M in
research grant income and investment. He is a co-inventor on 12 patent families with 80+
national filings covering applications in magnetic sensing, heating and actuation; and he is the
co-founder of three spinout companies: Endomagnetics Ltd (Apr. 2007); Resonant Circuits
Limited (Sept. 2009); and MediSieve Ltd (Apr. 2014). Together, these companies employ more
than 25 full-time staff; and one of them, Endomagnetics Ltd, recorded an annual turnover in
2017/18 of more than £6.0M.
Quentin was born and raised in New Zealand, and has lived in England since 1983. He is married
and has two daughters.
The tumor immune microenvironment is reshaped after systemic exposure to
magnetic iron oxide nanoparticles: A study in mouse models of breast cancer
Preethi Korangath, James Barnett, Anirudh Sharma, Elizabeth Henderson, Jacqueline Stewart,
Shu-Han Yu, Sri Kamal Kandala, Chun-Ting Yang, Mohammad Hedayati, Todd Armstrong,
Elizabeth Jaffee, Cordula Gruettner, Xian C Zhou, Wei Fu, Chen Hu, Saraswati Sukumar, Brian
W Simons and Robert Ivkov
Associate Professor, Radiation Oncology and Molecular Radiation Sciences
The factors that influence selective accumulation of nanoparticles into solid tumors remain an
area of intense interest. Five tumorigenic human breast cancer cell lines with varying HER2
status were used to grow orthotopic mammary tumors in nude and NOD/SCID gamma (NSG)
mice. A human HER2 overexpressing (huHER2) transgenic mouse (Genentech) was used to
develop a syngeneic allograft model that was implanted across FVB/N (immune competent),
nude, and NSG mice for comparative studies of tumor retention of nanoparticles. Starch-coated
bionizednanoferrite (BNF) nanoparticles labeled with trastuzumab (BNF-HER), unlabeled
(BNF-Plain), or PBS (control) were injected into tail veins of mice when tumors had a measured
volume of ~150 mm3. 24 hrs following intravenous injection, mice were sacrificed and tissues
harvested for analysis.
We demonstrate using inductively coupled plasma mass spectrometry and extensive
histophathology analysis that unlabeled starch-coated magnetic iron oxide nanoparticles showed
little accumulation in tumors regardless of tumor model or host strain. Surprisingly, retention of
BNF-HER nanoparticles was evident across all tumor models, with little variation among the
models. Further analysis showed that retention of the antibody-labeled counterpart in tumors
depended more on immune status of the host than on presence of the target antigen.
In vitro, a TH1-type activation of murine macrophages and neutrophils led to preferential uptake
of antibody-conjugated nanoparticles, suggesting nanoparticle retention in tumors was
determined by an inflammatory tumor-microenvironment. In the immune competent huHER2
allograft model, accumulation of plain nanoparticles was minimal as observed in human
xenograft models. Conversely, retention of BNF-HER nanoparticles in FVB/N mice bearing
huHER2 tumors was dramatically higher than in nude or NSG mice bearing this tumor, with
tumor retention occurring primarily in tumor-associated dendritic cells, neutrophils, monocytes,
and macrophages as determined by magnetically sorted flow cytometry. An intact immune
system with competent TH1 activation displayed preferential retention of antibody-labeled BNF
nanoparticles.
Systemic exposure of immune intact allograft (implanted) huHER2 models to either plain or
trastuzumab-labeled BNF nanoparticles delayed tumor growth and caused CD8+ T cell
infiltration fourteen days after injection.
These findings demonstrate that the immune microenvironment of solid-cancer tumors can be a
dominant factor that determines nanoparticle retention in tumors, and that systemic exposure to
nanoparticles has potential to initiate systemic immune responses leading to adaptive immune-
mediated tumor growth inhibition.
Our results show that nanoparticle constructs offer anti-cancer immune-modulating potential that
can be exploited for cancer immune therapy.
Robert Ivkov
Dr. Robert Ivkov is an assistant professor of radiation oncology and
molecular radiation sciences and oncology at the Johns Hopkins
University School of Medicine. His research interests include the
development, characterization, and use of nanomaterials to target
cancer and to enhance the effectiveness of current therapies such as
radiation. He has a particular focus of selective heating with
magnetic nanoparticles. Dr. Ivkov earned his M.D. and Ph.D. in
physical chemistry from the University of Maryland and his M.Sc.
from the University of Toronto, with an emphasis on
thermodynamic properties of proteins. He continued to perform
basic materials research at the National Institute of Standards and
Technology, and later moved to the private sector to develop oncology products. Prior to his
arrival to Johns Hopkins, Dr. Ivkov was vice president of research and development and a co-
founder of Triton BioSystems, Inc., a company developing targeted nanotherapeutics for
oncology.
Long term fate of iron oxide nanoparticles in the body: a long and
comprehensive survey
Florence Gazeau
MSC Université Paris Diderot/CNRS, USPC, Paris, France
Iron oxide nanoparticles (IONPs) are among the most promising nanomaterials in biomedicine
mostly due to their unique magnetic properties but also to their biocompatibility and
degradability. However, some questions remain on their long-term fate and biotransformation in
the organism. How long will the nanoparticles keep their magnetic properties and be useful for
applications? Where does the degradation take place? What are the mechanisms? What is the fate
of degradation products? Is there any recycling and transfer between organs? What is the journey
of the different particle components, the core and the shell? Which biological
response/adaptation to IONP overload and degradation?
I will present some of our latest results regarding the fate of different types of IONP in mice.
A part of my talk will focus on a possible pathway for metabolizing IONP degradation products
through a protein involved in iron metabolism, the ferritin. We have studied, in solution, the
degradation processes of iron oxide nanoparticles in the presence of ferritin proteins as well as
the iron transfer processes from nanoparticles to ferritin. The difficulty is the high concentration
of endogenous iron which makes it impossible to demonstrate such transfers in vivo. Thus, we
have developed a strategy to track these phenomena in vivo by doping iron oxide nanoparticles
with a scarce element in the organism, such as cobalt. This work highlighted a possible
mechanism of biological recycling, remediation and detoxification of metal oxide nanoparticles
mediated by endogenous proteins at the molecular scale. We also developed a multi-scale
method to study the life cycle of iron oxide nanoparticles and their by-products in the organism.
The main challenge is to differentiate iron steming from the nanoparticles from endogeneous
iron. This specific tracking problem is routinely encountered in geochemical studies and solved
by labelling the target material with minor stable isotopes. Therefore, iron oxide nanoparticles
enriched in the minor stable isotope 57
Fe were synthetised and injected intravenously in mice to
follow dynamic circulations of iron oxide nanoparticles and their by-products over a period of
six months. We have also labelled the particle coating to track the integrity of nanoparticles over
time and decipher the specific fates of inorganic core and organic shell. Results of this
comprehensive in vivo study will be discussed together with modifications of gene expression
related to the presence, accumulation and degradation of IONPs at different doses and in
different organs. Comparison with different types of materials, e.g. gold nanoparticles, will be
highlighted.
Florence Gazeau
Florence Gazeau, PhD in Physics 1997, University Paris Diderot, is
senior scientist in CNRS. PI of the Biother group (http://biother.net),
she is recognized in the domain of nanomagnetism and
nanomedicine. Her research interests include imaging and
therapeutic applications of activable nanoparticles, nanotoxicity,
life-cycle and long-term fate of nanoparticles, mechanobiology of
cancer, regenerative medicine and extracellular vesicles for
regenerative medicine and drug delivery. She is deputy director of
the laboratory Matière et Systèmes Complexes (MSC) at USPC
(Université Paris Diderot/CNRS) and one of the leaders for the
creation of MSC Med laboratory (Université de Paris 2019). She is author of more than 136
publications (h-index of 46, citations >7500), inventor of 6 pending patents and cofounder of
EverZom start up for the production of Extracellular Vesicles.
Translational requirements for nanotechnology enable medical products
Adriele Prina-Mello1,2,3
1 Department of Clinical Medicine, Trinity College Dublin, James’s Street, Dublin 8, Ireland
2 Laboratory for Biological Characterisation of Advance Materials (LBCAM) and Nanomedicine
Group, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin 8, Ireland 3 Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) Institute and
AMBER Centre, Trinity College Dublin, College Green, Dublin 2, Ireland
Pre-clinical assessment of nanomaterial is a key process for nanotechnology enabled medical
products. To maximise effort and costs, a successful multiparametric pre-clinical assessment
cascade is needed. Consideration for similarities between the pre-clinical and clinical screening
are draw up assessing industrially relevant aspects such as safe- and quality- by-design across the
critical steps that lead to product market approval. Starting from the physical and chemical
characterisation, to the specific theranostics properties, SuperParamagnetic Iron Oxide Nano
Particles (SPIONS) are presented as one of the most promising theranostic nanomaterial for
clinical application. Thus, the use of screening platforms, based on cell-nanoparticle mechanism
of biological interaction, are introduced for cost-effective go/no go assessment; these comprising
sterility, endotoxicity, cytotoxicity, and immunotoxicity. In vivo testing strategies, for specific
theranostic applications, are fundamental during the translational process. Finally, consideration
on past and present clinically translated products highlights the importance in developing
multiparametric pre-clinical experimental testing strategies focused on achieving sounds and
robust dataset for clinical translation.
Adriele Prina-Mello
Dr Adriele Prina-Mello is currently working as ussher Assistant
Professor in Translational Nanomedicine at Trinity College Dublin,
University of Dublin and part of the League of Universities (LERU).
His track-record in nanomedicine products translation from bench to
bedsite, and expert in R&D and scientific regulatory aspects
associated with nanotechnology-driven products. Key achievements
of Dr Prina-Mello are: Director of the LBCAM (Laboratory for
Biological Characterization for Advance Materials Director), aimed
at developing clinically and industrially interdisciplinary R&D in
the Biomedical and Healthcare area. He is also principal Investigator
at AMBER centre (Advanced Materials and BioEngineering Research Centre) and CRANN
institute (Trinity Nanoscience) European Technology Platform for Nanomedicine Executive
Board member and (2017-2019) Chair of the Education and Training working group, former
chair of Characterization and Toxicology group (2015-2017). European Commission Expert in
Characterization/Member of the European Materials Characterization Council. His scientific
interests are: Focused on advanced technology and materials translational research in
NanoMedicine (in vitro/in vivo diagnostic, imaging and therapeutics), Theranostics, Lab-on-a-
chip, Medical devices and Tissue engineering applications. Industrial and EC Track Record:
Member of several initiatives and association focused on the safe development of Translation of
Medicines and their industrialization. Since 2011 assisted translation of 6 technology platforms
from bench to bedside. Dr Adriele Prina-Mello was involved in several EC-H2020 and FP7
projects among these EU-NCL, REFINE, BIORIMA, NoCanTher, AMCARE, MULTIFUN,
NAMDIATREAM and others. Scientific Track Record: h-index: 29; citations:2787, author of
more than 100 peer-reviewed works, 8 book chapters, Associated Editorial Member of Precision
Nanomedicine, Scientific Reports and Cancer Nanotechnology (Springer-Nature Publishing). To
date delivered more than 50 keynote presentations in Nanotechnology for Medicine.
Nanoparticles for Molecular Imaging and Therapy
Holger Grüll
Department of Radiology, University Hospital of Cologne, 50937 Cologne, Germany
Nanomedicine, the application of nanotechnology to healthcare, offers new clinical solutions in
medical imaging and therapeutic applications. New nanomedicine material concepts allow the
design of more powerful, multipotent agents of sizes ranging from nanometers to microns, with
new properties and functionalities. These multi-potent particles will serve for example
applications as contrast agents in medical imaging for improved in-vivo diagnostic or enable new
applications such as spectral CT or magnetic particle imaging or ultrasound triggered local drug
delivery at the site of disease. A prerequisite are multifunctional nanoparticles that are tailored
towards their application but also take biological requirements into account.
In this presentation, some basic aspects of in vivo behavior of nanoparticles are discussed with
respect to biodistribution, excretion pathways and biological barriers they have to overcome. As
an example, work related to nanoparticles for CT imaging as well as magnetic nanoparticles for
magnetic particle imaging will be presented. Finally, an outlook will be given with respect to
application and medical approval of nanoparticles in medicine.
Holger Grüll
Holger Grüll studied chemistry in Cologne, Germany, and gained
1996 his PhD in Physical Chemistry. After his PhD, he was working
several years as postdoc and guest researcher at the Ben-Gurion
University of the Negev, Beer Sheva (Israel), the National Institute
of Standards and Technology (NIST) in Gaithersburg (USA), and
again the Ben-Gurion University of the Negev working on polymers,
nanoparticles, biomimetic membranes and drug delivery systems. In
2000, he started his career at the Philips Research Laboratory in
Eindhoven, The Netherlands, and became later responsible for the in
vivo research on molecular imaging and therapeutic applications. In
2007, Dr. Grüll was appointed professor at the Eindhoven University of Technology holding a
chair for Molecular Imaging and Image-guided Interventions. In 2016, Dr. Grüll received an
appointment full professor at the department of radiology, University Hospital Cologne, where
Dr. Grüll is heading the laboratory for experimental imaging. Main research areas are
nanoparticles for imaging applications and drug delivery with main focus on high intensity
focused ultrasound applications, temperature sensitive liposomes, magnetic nanoparticles and
particles for spectral CT application in cancer.
Monocore or multicore iron oxide nanoparticles synthesized in polyols and
coated with a thermosensitive cell-penetrating peptide
Olivier Sandre1, Gauvin Hémery
1, Emmanuel Ibarboure
1, Elisabeth Garanger
1, Sébastien
Lecommandoux1, Pauline Jeanjean
2, Coralie Genevois
2, Franck Couillaud
2, Sabrina Lacomme
3,
Etienne Gontier3, Ashutosh Chilkoti
4
1 LCPO UMR5629 Univ Bordeaux, CNRS, Bordeaux INP, ENSCBP, Pessac, France
2 IMOTION EA7435 Univ Bordeaux, Bordeaux, France.
3 BIC UMS3420 Univ Bordeaux, CNRS, Inserm, Bordeaux, France.
4 Biomedical Engineering, Duke University, Durham, NC, United States.
This communication reports the grafting onto iron oxide nanoparticles (IONPs) of recombinant
polypeptides made of di-block elastin-like peptide (ELP40-60) and cell-penetrating peptide (Tat)
sequence.1The ELP40 block is thermosensitive and undergoes a water de-swelling transition at a
critical temperature around 42 °C in solution, the ELP60 block is hydrophilic and provides
colloidal stability to the resulting γ-Fe2O3@ELP40-60-Tat core-shell IONPs. Magnetic IONPs
were synthesized by a polyol pathway with either monocore (nanospheres) or multi-core
(nanoflowers) morphology, narrow size-dispersity and suitable heating efficiency under an
alternating magnetic field (AMF).2 The bio-functionalization of these IONPs with the di-block
ELP40-60-Tat was achieved by a convergent strategy through strong coordination bonding of a
phosphonate group introduced near the N-terminus of the polypeptide. To the best of our
knowledge, this is the first report on a thermosensitive ELPm-n polypeptide brush grafting onto
magnetic IONPs. Large temperature variations of the sample (up to 30 °C) could be obtained in a
few minutes by applying an AMF. Fast size changes of the magnetic core-thermosensitive shell
nanoparticles were measured by in situ dynamic light-scattering (DLS) while the AMF was on.
Variations of the hydrodynamic size were compared to the classical polymer brush model
revised for the highly curved surface of nanoparticles. Cellular internalization and toxicity assays
were performed on a glioblastoma (U87) human cancer cell line in view of applications for drug
delivery activated magnetically. Superior cellular uptake was observed in vitro for multicore
IONPs compared to monocore IONPs (for the same PEG coating),3 and for IONPs@ELP40-60-Tat
peptide-grafted nanoparticles compared to IONPs@PEG controls prepared from the same
(spherical) cores. The internalization pathway in lysosomes was monitored by electron
microscopy on microtomes and confocal optical microscopy on live cells. Cellular toxicity after
AMF application with these core-shell IONPs was ascribed to lysosomal membrane rupture and
leakage into the cytosol. The intra-cellular fate of such IONPs, from their internalization to the
effect of an AMF application, validates the use of thermosensitive peptide brushes on IONPs as
drug delivery systems, addressing lysosomal compartments and triggering leakage of their
content by external AMF application. Preliminary in vivo experiments evidenced the positive
1 E Garanger, S MacEwan, O Sandre, A Brûlet, L Bataille, A Chilkoti, S Lecommandoux, Macromol. 2015, 48, 6617
2 G Hemery, A Keyes, E Garaio, I Rodrigo, J A Garcia, F Plazaola, E Garanger, O Sandre, Inorg. Chem. 2017, 56,
8232 3 G Hemery, C Genevois, F Couillaud, S Lacomme, E Gontier, E Ibarboure, S Lecommandoux, E Garanger, O
Sandre, Molecular Systems Design & Engineering 2017, 2 629
effect of the Tat peptide end-sequence compared to the PEG brush control on the bio-
distribution, with similar contents in the liver and in U87 model tumor in mice. Long term fate
(after 48 h) is discussed in view of the cell division with equal sharing of the magnetically loaded
lysosomes among daughter cells, possibly envisioning the successive application of magnetic
hyperthermia on time scales superior to the cellular life cycle
Olivier Sandre
Dr Sandre Olivier is currently working as Senior CNRS researcher at
LCPO Univ Bordeaux /Polymer self-assembly & life sciences. Dr.
Olivier has defended PhD thesis of UPMC Université Paris 6
supervised by Pr. Françoise Brochard-Wyart at Curie Institute. He is
member of advisory panel of IOP journal Nanotechnology and
editorial board of MDPI Nanomaterials. Dr. Olivier received Young
Researcher 2012 Award of the Chemical Physics. He is chair of
CNRS Institute of Chemistry (2018-2023). Member (2013) and
Chair (2017-) of Condensed Matter Division board of the French
Physical Society (SFP), Member of RSC and Polymer Group GFP.
Current research of Dr. Olivier is focused on: Magnetic nanoparticles (synthesis and properties);
Polymer self-assemblies (micelles, vesicles…); Magnetically controlled drug release; Magnetic
hyperthermia; MRI contrast agents.
Magnetic nanomaterial as a mediator, carrier and trigger for hyperthermia-
complementing combined therapies of tumors: MagBioVin approach
Zeljko Prijovic
“Vinca” institute of nuclear sciences, University of Belgrade, Belgrade, Serbia
Effective heating of the super-paramagnetic nanoparticles (MNPs) by alternating magnetic field
(AMF) serves as a base for development of AMF-generated hyperthermia for tumor therapy.
Despite being thoroughly investigated by years and the basic idea confirmed in vitro, it is
sparsely used in clinics. The limitations arising from basic laws of physics, nature of the material
and interaction with biological systems hamper the applicability in vivo. Namely, resembling
some properties of viruses and bacteria, most of the MNPs encounter biological barriers and
immune system components when applied in vivo, leaving relatively small amounts of MNPs
capable of reaching the tumor. An opposite process, enhanced permeability and retention (EPR),
allows MNPs to reach the tumor and retain there. However, it is frequently not sufficient to
accumulate enough MNPs to effectively heat large volume of the tumor, hampering the use of
therapy. Also, nature of MNP-mediated hyperthermia limits the cells damage to short distance
only.
Combining our expertise in magnetism, radioisotopes, pharmacology and cancer biology in
project MagBioVin, we focused on improving all phases of the approach, aiming to generate
material and therapeutic approaches suitable for in vivo application. Aiming that goal, we have
been optimizing the preparation of MNPs and their coating by various compounds (citrate, PEG,
DOTA, dopamine, lysine etc…) to improves their circulation half-life, help avoiding immune
system, lower the toxicity and serve as a linker for radioisotopes, drugs and bio-macromolecules.
The produced material is screened for cytotoxicity and hyperthermia-induced cell death on
mouse and human cancer cell lines in vitro. Material with suitable characteristic serves as a base
for in vivo application.
Potential for tumor therapy of coated and derivatized MNPs have been tested in vitro measuring
its impact on cancer cells in tissue culture and in vivo on the impact on growth of mouse and
human tumor xenografts on immune-competent and immune compromised mice. The data
confirmed the basic mode of action but facing the same limitations as reported earlier. To
overcome them, we have been focused on developing combined therapies, by linking the MNPs
to agents complementing or synergizing hyperthermia, as radionuclides (131
I, 90
Y, 177
Lu, 99m
Tc…), anticancer drugs (camptothecins), signal molecules (IL12), antibodies (CC49/Tag72)
and enzymes (beta-Glucuronidase). The mechanism of action of the obtain material may have
better pharmacological and therapeutic effects, surpassing hyperthermia alone, justifying their
further development for eventual therapeutic approach.
Zeljko Prijovic
Dr Zeljko Prijovic received his PhD in biochemistry (medicinal
enzymology) at School of Chemistry, University of Belgrade.
Major focus of his work has been cancer research, more precisely
development of low toxic therapies of tumors. His specialties are
enzyme/prodrug therapies as Prodrug Monotherapy (PMT),
Antibody-, Virus- and Bacteria-Directed Enzyme-Prodrug
Therapies (ADEPT, VDEPT, BacDEPT), in vitro and in vivo tumor
models including human tumor xenografts and orthotopic tumors.
He has three patents regarding enzyme/prodrug therapy approaches
and won two prizes for development of new technologies for
pharmaceutical companies. After long-term engagement in Institute
of Biomedical Sciences, Academia Sinica, Taipei, Taiwan and School of Medicine, University of
Patras, Greece, he is recently engaged in Nuclear Institute Vinca as ERA Chairperson on a
project “Strengthening of the MagBioVin Research and Innovation Team for Development of
Novel Approaches for Tumors Therapy based on Nanostructured Materials” (MagBioVin).
Focus of the project is development of tumor therapies based on combination of magnetic
nanomaterial, radioisotopes and biomolecules to overcome some of limitations of application of
magnetic nanoparticles in oncothermia.
Magnetic nanoparticles aggregation effects on cellular magnetic hyperthermia
Maria Eugenia Fortes Brollo1, Patricia Hernandez Flores
2, Lucía Gutiérrez
3, Domingo F. Barber
2
and María del Puerto Morales1
1 Department of Energy, Environment and Health, Institute of Material Science of Madrid
(ICMM-CSIC), Madrid, Spain 2 Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de
Biotecnologıa, (CNB-CSIC), Madrid, Spain 3 Department of Analytical Chemistry, Universidad de Zaragoza and CIBER-BBN, Instituto
Universitario de Nanociencia de Aragon (INA), Zaragoza, Spain
Aggregation processes of magnetic nanoparticles in biosystems are responsible for alteration of
their performance in vitro and in vivo due to the modification of their magnetic properties1. Here
we present a systematic study using different nanoparticle coatings, cell lines, subcellular
localizations, and nanoparticle core sizes, in an attempt to isolate the source of the high
variability of the results obtained from different studies on cellular magnetic hyperthermia2. We
have also developed models mimicking the aggregation degree and the spatial distribution of
nanoparticles in biosystems (magnetoliposomes) and compare their magnetic properties with that
of real biological examples (cells incubated with nanoparticles)3. The results indicate that the
simple fact of being in contact with the cells makes the nanoparticles aggregate in a non-
controlled way, which is not the same aggregation caused by the contact with the cell medium
nor inside liposomes. These results could explain bibliographic data on the heating efficiency
and MRI relaxivity changes for nanoparticles in contact with the cells.
María del Puerto Morales
María del Puerto Morales is Professor at the Institute of Material
Science in Madrid (ICMM/CSIC), Spain since 2008. She got her
degree in Chemistry by the University of Salamanca in 1989 and her
PhD in Material Science from the Madrid Autonomous University
in 1993. From 1994 to 1996, she worked as a postdoctoral fellow at
the School of Electronic Engineering and Computer Systems of the
University of Wales (UK) and got her permanent position at the
ICMM/CSIC in 2000 (4 Sexenios). Her research activities are
focused on the area of nanotechnology, in particular in the synthesis
and characterization of magnetic nanoparticles for biomedicine,
including the mechanism of particle formation,surface modification and its performance in
biomolecule separation, NMR imaging, drug delivery and hyperthermia.
1Etheridge et al., Technology, 2(3) (2014), 214-228 2Brollo, et al. Phys. Chem. Chem. Phys., 20 (2018) 17829-17838. 3Mejias et al., ACS Appl. Mater. Interfaces, 11(1) (2019) pp 340–355
She has authored several book chapters in the field of nanoparticle synthesis (9), patents (3) and
200 articles in interactional scientific journals (h=51, >10.500 citations). She has been the
principal investigator from the CSIC in two European-funded research projects in the 7FP
(Multifun and NanoMag) and is participating in one FET-OPEN, HOTZYMES 2019-2021. She
has also participated in other 30 national projects, has supervised 5 thesis and 1 more is on-
going, and has presented more than 30 invited talks at conferences.
Chemically Engineered Iron Oxide Nanocrystals for Transport of
Biomolecules Across Biological Barriers
Isabel Gessner, ShaistaIlyas, Eva Krakor, Laura Wortmann and Sanjay Mathur
Chair, Inorganic and Materials Chemistry University of Cologne, Greinstrasse 6, D-50939
Cologne, Germany
Chemical processing of functional ceramics has played a key role in converging disciplines,
which is especially true for their bridge-building role in integrating the concepts of inorganic
materials synthesis with biomedical applications. Out of a vast variety of metal and metal oxide
nanoparticles that have been developed for medicinal purposes, iron oxides are one of a few
materials that made it through clinical trials. Due to their high biocompatibility, stability and the
abundance of iron in our environment, which results in low costs of iron-based materials, diverse
iron oxide nanoparticles (IONPs) have been prepared for biomedical applications. In our
workgroup, ɣ-Fe2O3, α-Fe2O3 and Fe3O4 based IONPs have been synthesized using a broad range
of well-established synthetic procedures. By changing the reaction conditions and applying
suitable surface ligands, the morphology (spherical, cube-shaped, ellipsoidal), surface charge and
dispersibility of IONPs could be tuned according to the desired application allowing for a
reproducible fabrication of optimized and highly efficient vectors. Controlled surface
vectorization with biomolecules led to the formation of cancer targeting platforms, while the
employment of the highly selective click chemistry enabled the magnetic separation of proteins
out of a proteome mixture. Moreover, as-prepared particles could be used for drug delivery
applications, either through covalent attachment of a drug to the particle surface or by using the
IONPs as templates to prepare hollow drug containers. This talk will present how chemically
grown nanoparticles can be transformed into bio-vectors for magnetic resonance imaging (MRI)
and drug delivery applications.
Sanjay Mathur
Professor Sanjay Mathur is the Director of the Institute of Inorganic
Chemistry at the University of Cologne in Germany. He is also the
Director of the Institute of Renewable Energy Sources at the Xian
Jiao Tong University, Xian, China and a World Class University
Professor at the Chonbuk University in Korea. He is a Visiting
Professor in the Institute of Global Innovation Research at TUAT.
He also holds Visiting Professorships at the Central South
University, China and National Institute of Science Education and
Research, India. His research interests focus on application of
nanomaterials and advanced ceramics for energy technologies. He
holds ten patents and has authored/ co-authored over 430 original research publications and has
edited several books. He is a Titular Member of the International Union of Pure and Applied
Chemists (IUPAC) and a member of the ISO Technical Committee on Nanotechnologies. He
serves as the Editor for Journal of Electroceramics, and as the Principal Editor of J. Mater.
Research. He is also an Associate Editor for NanoEnergy, International Journal of Applied
Ceramics Technology, International Journal of Nanoscience and Nanomaterials. He is also on the
Editorial Boards of journals International Journal of Nanotechnology, Materials, Journal of
Ceramic Science and Technology. He was awarded the Honorary Doctorate of the Vilnius
University in 2016. He is an Academician of the World Academy of Ceramics and Fellow of the
American Ceramic Society. He also acts as the “International Ambassador” of the University of
Cologne. He is the recipient of the Global Star and Bridge-Building awards of the American
Ceramic Society, Lee Hsun award of the Chinese Academy of Science and Surface Innovator
Award of the SSPC and AkzoNobel. He is a member of the Advisory Board of the Federation of
German Materials Science (DGM) and also serves on the Board of the German Chemical
Industries Network CHEMCOLOGNE. He is on the Review Advisory Panel of the CSIR, South
Africa and serves as International Advisor to Korean Institute of Industrial Technology
(KITECH), Incheon, Korea and Vice-President of the Thin Film Society, Singapore. He is on the
ACerS Board of Directors. He has been elevated to the ASM class of fellows of 2017. He is the
Chair of the Kavli Awards Subcommitee of the Materials Research Society. Since 2018, he also
chairs the Academic Affairs Committee of the Materials Research Society.
Meccanotransduction of axonal growth: a new strategy based on
magneticnanoparticle to romote nerve regeneration
Vittoria Raffa
Università di Pisa, Department of Biology. Pisa, Italy
Axonal growth is a complex mechanism and, recently, it has been elucidated that mechanical
forces play an important role. The so-called "stretch-growth model" has been proposed as an
alternative to the more widely recognized "tip-growth model". According to the "stretch-growth
model" elongation is induced by mechanical stimuli, whether these come from the growth cone,
or originate from different stimuli such as body growth or the use of exogenous mechanical
forces. However, this model is not yet accepted as a universal model of axonal growth, because
some contradictions have emerged. The main one consists in the fact that some literature has
highlighted the presence of a threshold value to overcome so that the mechanical force can
stimulate the elongation of the axon. Nevertheless, this threshold value is higher than the tension
generated at the growth cone and this is why it has been questioned if the "stretch growth model"
is valid in physiological conditions. However, the tools previously used to investigate the effects
of mechanical stress had limits regarding sensitivity and reliability, which makes them unusable
to study tensions below 100 pN. To overcome this problem, we have labelled neuron-like cells
and primary neurons by magnetic nanoparticles for the generation of a weak force, which may
vary, under the action of an external magnetic field, from 0.1 to 10 pN. We demonstrate that
neurite elongation proceeds at the same previously identified rate, on application of mechanical
tension of ~ 1 pN, which is significantly lower than the force generated in-vivo by axons and
growth cones. This observation raises the possibility that mechanical tension may act as an
endogenous signal used by neurons for promoting neurite elongation.
Vittoria Raffa
Vittoria Raffa has an established international reputation by virtue
of the original publications on medical aspects of nanotechnology
and nanomedicine. She was author in the last 10 years of 60
publications in ISI journals (h-index 24, total citations 2200) and 5
patents on technologies relating to nanomedicine. She is Associate
Professor of Molecular Biology, Ph.D. in Nanotechnology, M.Sc. in
Chemical Engineering. From 2014 to 2016 she was Professor at the
University of Dundee (UK) and PI of Nanobio Lab (School of
Medicine, Dundee, UK). Currently, she is Professor at the
University of Pisa; lecturer of 2 courses related to Molecular
Biology and 2 courses related to Nanomedicine; leader the Nanomedicine Lab of the Department
of Biology (UNIPI, IT). The Nanomedicine Lab is a very multidisciplinary environment, with
people working at the interface of different disciplines in Life and Physical Sciences. Her long-
term research interests are in the field of neuroscience and in the study of the
mechanotransduction of axonal growth.
Nanomagnetic approaches for vascular healing and cardiac regeneration
Boris Polyak
Department of Surgery, Drexel University College of Medicine, Philadelphia, USA
Magnetic nanoparticles and various magnet systems have been used in a range of applications
aimed to achieve localized delivery of therapy and tissue regeneration. For local delivery of
therapy, magnetic carriers associated with drugs, nucleic acids or loaded within cells are directed
or guided by magnetic forces towards certain biological targets. The magnetic delivery of
therapeutic agents results in the concentration of the therapy at the target site, consequently
improving therapy delivery efficiency while reducing or eliminating the systemic therapy side
effects. For tissue regeneration, magnetic nanomaterials are used in remotely controlled actuation
for the release of bioactive molecules or mechanical conditioning of cells to generate tissue
constructs for restorative tissue support or reconstruction. Mechanical conditioning of cells and
tissue constructs is an important factor in determining the properties of the tissuebeing produced.
This conditioning is particularly relevant to the generation of vascularized cardiac muscle, where
mechanical stress activates mechano-sensitive receptors, triggering biochemical pathways that
promote the production of functional tissue. This talk will present two applications where the
magnetic approach has the potential to enable tissue restoration or support. One example will
present an innovative method that takes advantage of magnetic nanoparticles and intravascular
steel stents to deliver endothelial cells to the blood vessels with the ultimate aim to repair the
injured artery. Another study will present a novel strategy for creating a vascularised and
functional tissue graft by combining the use of a macroporous alginate scaffold impregnated with
magnetically responsive nanoparticles in combination with non-invasive magneto-mechanical
stimulation. While a distinct mechanism underlines the strategies described in each example,
both cases demonstrate versatile capabilities of magnetic systems for regenerative applications.
Boris Polyak
Dr. Polyak earned his Ph.D. in Biotechnology Engineering in 2004
from the Ben-Gurion University, Israel specializing in biological
sensors. In 2007, Dr. Polyakcompleted his postdoctoral training at
the University of Pennsylvania, Children’s Hospital of Philadelphia
where he has been developing methods for gene and cell delivery to
magnetizable implants. The goal of our group is to explore the
multiple interfaces between materials science, chemistry, and life
science. A major focus is on applications of magnetic phenomena
in medicine, including targeted drug delivery, tissue engineering,
andbioimaging. Dr. Polyak has received research and educational
funding from NIH, W.W. Smith Charitable Trust, Stein Foundation, Bi-National US-Israel
Science Foundation, and the State of Pennsylvania. His teaching focuses on drug delivery
systems and engineering of advanced materials for regenerative applications.
Thermal therapies mediated by iron oxide-based nanoparticles: quantitative
comparison of heat generation, therapeutic efficiency and limitations
Ana Espinosa1,2,3
I MDEA Nanociencia, c/Faraday, 9, 28049 Madrid, Spain
2 LaboratoireMatière et Systèmes Complexes, UMR 7057, CNRS
and University Paris Diderot, 75205 Paris cedex 13, France 3 Instituto de Ciencia de Materiales de Madrid, Consejo Superior deInvestigacionesCientíficas,
Cantoblanco, E-28049 Madrid, Spain
Thermal nanotherapies as magnetic hyperthermia (MHT) and photothermal therapy (PTT) are
two promising emergent treatments and non-invasive approaches for tumor ablation, where
localized heat generation is mediated by magnetic and photo-activatable nanomaterials12
. Until
very recently, these thermal nanotherapies, have been developed separately: MHT is mainly
focused on the use of magnetic iron oxide nanoparticles due to their excellent biodegradability3,
while metallic nanoparticles such as gold nanomaterials are often preferred due to their strong
absorption cross sections. They have recently begun to intersect due to the recent discovery and
use of photothermal properties of iron oxide nanostructures4 or to the use of magneto-
photothermal hybrids5, which efficiently combine both heating features in one-single object.
A comprehensive comparison of the heating efficiency of magneto- versus photo-thermal effect
is presented, where different magnetic nanoparticles have been confronted (iron oxides, cobalt
ferrite, spheres, cubes, flowers) with different metallic nanoparticles in aqueous, cellular, and
tumoral environment6. Intracellular processing markedly impacted MHT, while endosomal
sequestration could have a positive effect for PTT. In the search for the most therapeutically
viable modality, the effect of nanoparticle concentration and the experimental exposure
parameters (magnetic field strengths/frequencies and laser power densities) have been
investigated. The intracellular biotransformations of these nanomaterials in the biological
environment has also been explored through the study of their physical and chemical
modifications at the nanoscale over the time7.
Aknowledgements: MINECO project SEV-2016-0686 and Comunidad de Madrid 2018-T1/IND-
1005.
1R. Hergt and S. Dutz, J. Magn. Magn. Mater. 311, 187 (2007).
2 M. Garcia, Journal of Physics D: Applied Physics 44, 283001 (2011).
3A. G. Roca, L. Gutiérrez, H. Gavilán, M. E. F. Brollo, S. Veintemillas-Verdaguer, and M. del Puerto Morales, Adv.
Drug Deliv. Rev. (2018). 4A. Espinosa, R. Di Corato, J. Kolosnjaj-Tabi, P. Flaud, T. Pellegrino, and C. Wilhelm, ACS Nano 10, 2436 (2016).
5A. Espinosa, M. Bugnet, G. Radtke, S. Neveu, G. A. Botton, C. Wilhelm, and A. Abou-Hassan, Nanoscale 7, 18872
(2015). 6A. Espinosa et al., Adv. Funct. Mater. 28, 1803660 (2018).
7F. Mazuel, A. Espinosa, G. Radtke, M. Bugnet, S. Neveu, Y. Lalatonne, G. A. Botton, A. Abou‐Hassan, and C.
Wilhelm, Adv. Funct. Mater. 27, 1605997 (2017).
Ana Espinosa
After obtaining a PhD in the domain of wide band gap oxides for
applications in Information Technologies in 2010, AE worked as a
postdoctoral fellow at the Magnetism and Magnetotransport
Laboratory (ICMM-CSIC, Spain) on the study of structural and
magnetic properties of nanoparticle systems. In 2013, she joined the
Laboratoire de Matière et Systèmes Complexes (MSC, France) to
conduct a research activity based on nanotherapies for cancer
treatment by means of thermal effect (magnetic and plasmonic
hyperthermia) as an Intraeuropean Marie Curie postdoctoral fellow.
In 2017, she moved to the Materials for Health group (CSIC, Spain)
with the aim of studying different synthesis protocols of nanostructures for magnetic
nanotherapies. Recently, AE has joined the IMDEA Nanoscience (Spain) research center to
study multifunctional strategies based on magnetic and photothermal nanoplatforms for cancer
treatment.
On the feasibility of improving heat production in magnetic fluid
hyperthermia: the time of topology
Gerardo F. Goya
Departamento de Física de la Materia Condensada & Instituto de Nanociencia de Aragón,
Universidad de Zaragoza, Zaragoza, Spain
The use of magnetic nanoparticles (MNPs) as nanosized sources of intracellular heat to fight
cancer, a therapy known as Magnetic Fluid Hyperthermia (MFH), relies on the capacity of MNPs
to heat cancer cells up to temperatures of 42-46ºC by a remote radiofrequency magnetic field.
Although already applied in clinical protocols, there is still a lot of room in MFH to further
improve the heating efficiency, a desirable goal in order to lower the administered doses of
MNPs while keeping their therapeutic efficacy. It has become clear along the last years that
under physiological conditions, the power absorption is hindered by different effects like
agglomeration, changes in local viscosity and pH within the cell, attachment to membranes, etc.
Quite a lot of effort has been applied to understand how each one of these impairments can be
overcome and make the MNPs to heat regardless of their physicochemical environment. The
formation of low-dimensionality arrangements of single-domain MNPs is being considered lately
as a possible way to use magnetic dipolar interactions to increase the power absorption by Néel
relaxation. It has been reported that linear structures such as elongated clusters or chains can
raise the values of the specific power absorption of MNPs. These structures have been
theoretically modeled and it is now apparent that new magnetic phenomena are in place and
require unequivocal experimental data in order to understand the complex magnetism of these
systems. Our recent work addressed the issue of how agglomeration of MNPs in vitro affects the
heating efficiency, and how the induced formation of low dimensional structures can improve it.
We have observed that systematic data from naturally agglomerated MNPs in gel and resin
phantoms can be compared to well-characterized clusters formed within the cytoplasm of
cultured cells. We found clear evidence that MNPs clusters grown under DC applied fields have
lower fractal dimension than the corresponding control cells, and the resulting heating rates
increased both in synthetic phantoms and within cells. The experimental data and numerical
modelling support the idea that magnetic dipolar interactions can be maneuvered to increase the
effective heating efficiency of the MNPs within cells.
Gerardo F. Goya
Dr. Gerardo F. Goya (Argentina, April 1964) completed his PhD
degree at the University of La Plata and Centro Atómico Bariloche,
Argentina. During 2001-2007 Prof. Goya has been Associate
Professor at the Institute of Physics, University of Sao Paulo
(Brazil), where he created and managed the mechanochemistry
laboratory at the Materials Physics Department (DFMT).
Dr. Goya is currently Associate Professor at the University of
Zaragoza, Spain, where he joined the Institute of Nanoscience of
Aragón (INA) in 2005 to start and consolidate a new research line
on nanomagnetism and biomedical applications of magnetic
nanoparticles, mainly magnetic hyperthermia. The achievements in
this period include new methods of synthesis of magnetic NPs with
improved control of size and magnetic properties, and the successful
proof of principle of a ‘Trojan Horse strategy’ for oncology, by inducing cell death with
magnetic hyperthermia in dendritic-cell primary cultures. In addition, the group has developed
several studies of different biological agents as models of interaction with magnetic particles.
Prof. Goya led the design, development and building of a unique equipment for measuring power
absorption in magnetic hyperthermia. This was a pioneer system with many technological
improvements designed to make a fully automatic measuring system. The innovation of these
activities made the basis for a spin off company from the University of Zaragoza, of which he is
co-founder and scientific advisor. He has more than 150 international publications (h-index=36)
with more than 5000 citations, 2 PCT patents and more than 120 conference presentations
including more than 40 invited talks. His work has established an internationally recognized
research group in biomedical applications of magnetic nanoparticles, composed of engineers,
biologists, chemists, and physicists. In collaboration with top-level parasitologists,
immunologists and medical doctors, the group has managed to consolidate a common platform in
biomedicine, which is reflected in the coordination of highly innovative multinational projects.
Graphene oxide functional nanohybrids with magnetic nanoparticles for
improved vectorization of anticancer therapeutics
Giuseppe Cirillo
University of Calabria, Department of Pharmacy, Health and Nutritional Sciences, Rende, Italy
Nanographene Oxide (NGO) due to the hexagonal sp2-bonded carbon atoms lattices structure,
possessed superior electrical, chemical, physical, mechanical, and biological properties making
them attracting materials for the fabrication of highly engineered hybrid nanocarriers. Such
materials, resulting from the combination with polymers from both synthetic and natural origin,
are receiving increasing attention in biomedicine. We recently proved that the functionalization
of the polymer counterpart with polyphenol compounds is a valuable strategy to obtain of a
functional drug delivery system, in which the biological effect is related to both the loaded drug
and the carrier itself. A further improvement was achieved by functionalization with magnetic
nanoparticles, with the possibility to target the payload at the proper site. In this presentation, we
combined graphene oxide, iron oxide nanoparticles, and a newly synthesized human serum
albumin–curcumin conjugate for the fabrication of a multifunctional nanohybrid to spatially
control the vectorization of doxorubicin to neuroblastoma SH-SY5Y cells. Each component
contributed to the performance of the final nanohybrid: (1) magnetic nanoparticles act as a
targeting element; (2) NGO enhances the drug loading capability and makes the release profile
prolonged over time; and (3) immobilized curcumin in the functional coating synergizes the drug
cytotoxicity. The effectiveness of the proposed system is tested by a multidisciplinary approach,
which combines expertise in materials science, chemistry, biology, and oncology.
Giuseppe Cirillo
Giuseppe Cirillo (Italy, June 1980) completed his PhD degree in 2008
and currently works in the fields of Materials Science, Pharmaceutical
Technology and Macromolecular Chemistry at Department of Pharmacy,
Health and Nutritional Sciences, University of Calabria (Italy). The
interest in nanomedicine was implemented during the post-doctoral
fellowships at University of Calabria from 2009 to 2016 in cooperation
with IFW Dresden where he was visiting researcher. During this period,
further cooperation were established at an international level focusing on
the development of polymer therapeutics and multi-functional hybrid
materials for biomedical and pharmaceutical applications. He has more
than 100 publicationsin ISI journals (h-index=30, total citations 2500). He achieved the National
Qualification as Associate Professor in Drug technology, socioeconomics and regulation and in
the Chemical basis of Technology Applications in 2012 and 2016. He was lectures on Chemistry
and Biochemistry of Fermentations; Innovative Drug Delivery Devices; and Pharmaceutical
Technology.
Engineering and optimization of Specific Absorption Rates of Fe
oxidenanoparticles in magnetic hyperthermia
V. Kuncser1, N. Iacob
1, A. Kuncser
1, P. Palade
1, C. Comanescu
1, R. Turcu
2, G. Schinteie
1
1 National Institute of Materials Physics, 077125, Bucharest-Magurele, Romania
2 National Institute of Isotopic and Molecular Technologies, Cluj-Napoca, Romania
Issues related to the magnetic response of complex systems consisting of different types of Fe
oxide nanoparticles (with different shapes and aspect rations, non-interacting or forming
assembles, etc.) with respect to magnetic hyperthermia effects are emphasized together with
proposed theoretical and experimental solving items. Specific characterization methodologies
based on temperature and field dependent Mössbauer spectroscopy and SQUID magnetometry
deserving an adequate magnetic characterization of the nanoparticulate systems in respect to
phase composition, local and long-range magnetic structure, intra- and inter-particle magnetic
interactions and mainly to the magnetic relaxation phenomena of interest for heat transfer
mechanisms in magnetic hyperthermia are underlined. The different methodologies for the
correct evaluation of the specific absorption rate (SAR) from real experimental data taking into
account also environmental loss factors are critically discussed. Micromagnetic simulations and
complementary analytical tools are used in order to search for optimal shapes and sizes of non-
interacting Fe oxide magnetic nanoparticles leading to enhanced specific absorption rates. A
specific attention is provided to the effects of inter-particle (dipolar type) interactions on the
magnetic relaxation effects in magnetic fluids of different volume fractions. It has been proven
by micromagnetic simulations that the direct effect of the inter-particle dipolar interaction is not
only an increased particle anisotropy energy but also a decrease of the characteristic time
constant τ0, with direct influence on the efficiency of the heat transfer during potential
hyperthermia treatments. Experimental determination of specific absorption rates on ferrofluids
with similar nanoparticles but of different volume fractions as well as in case of ferrofluids with
different shapes and size of nanoparticles are presented and discussed.
Victor Kuncser
Dr Victor Kuncser, is currently a Research Professor at The National
Institute of Materials Physics in Bucharest-Magurele
(http://www.infim.ro), Head of the Magnetism and
Superconductivity Department and a member of the executive board
of the Institute. He is PhD promoter as Professor associated to
University of Bucharest, Faculty of Physics.His previous
appointments and research secondments include: Rostock and
Duisburg Universities, University of Rouen, Padova and Zaragoza,
Deutsche Synchrotron and Berlin Neutron Scattering Center. Victor
received his PhD in Physics in 1995 at the Institute of Atomic
Physics, Bucharest-Magurele and has been awarded the Alexander von Humboldt fellowship in
2001 and the prize of the Romanian Academy in 2002. Victor published more than 200 scientific
papers in ISI quoted international journals, six book chapters and was coeditor of a Springer
book. His scientific interest is in the field of magnetic interactions and local phenomena in
intermetallics and oxides, molecular magnets, ferrofluids, magnetic nanocomposites,
multifunctional and magnetofunctional materials, thin films and multilayers.
Taking magnetic hyperthermia and magnetogenetics to the next level: key
aspects to address from a basic-physics point of view
David Serantes
Instituto de Investigacións Tecnolóxicas and Applied Physics Department, Universidade de
Santiago de Compostela, Santiago de Compostela, Spain
The aim of the talk is to highlight some key aspects that, in my opinion and from the theoretical
point of view, need to be addressed in order to achieve further biomedical success using the heat
released by nanomagnets under AC fields: despite the promising application perspectives
(hyperthermia cancer treatment; drug release; magnetogenetics; etc.), the fact is that the success
in reaching routine clinical practice is very scarce. From the physics point of view, a main
difficulty is the lack of theoretical models able to describe the behaviour of MNPs in the viscous
biological environment, what results in the absence of accurate tools able to guide the
experiments. The failure in the current models involves several key factors, including procedural
(complete impossibility to explain successful heating effects on cells when the global heating is
negligible); interpretative (current heating mechanisms cannot account for accurate heat-
triggering experiments – other mechanisms at play?); and descriptive ones (available models are
limited to short timescales, far from those of the experiments). The complex nature of the
problem requires a multiphysics approach to go beyond the state-of-of-the art and overcome the
above limitations, able to; simultaneously embrace superparamagnetic and Brownian processes;
provide alternatives to current heat generation mechanisms; and efficiently deal with the
different timescales involved. During the talk I will try to summarize the limitations and a
possible approach to overcome them, with the objective of developing of a general framework
for the comprehension of the heating performance of magnetic nanoparticles under AC magnetic
fields in viscous media.
David Serantes
David Serantes currently holds a combined teaching and research
position at the Universidade de Santiago de Compostela (USC) in
Galicia, Spain. His expertise is on theoretical nanomagnetism, being
his research characterized by a strong interaction with
experimentalists. He obtained his PhD on magnetocaloric properties
in nanosystems at the USC in 2011; then as a postdoc he joined the
ICMM (Madrid, Spain) to work on ultrafast magnetisation
dynamics. Since then, his work is focused on the study of magnetic
nanoparticles for biomedical applications. Particularly, he studies
their response under external AC fields to be used as heat mediators
for biomedical applications, as hyperthermia cancer treatment (second postdoc at the University
of York, UK) or the remote magnetogenetic control of cellular activities (core of his current
project). His investigation involves the development of new theoretical models, requiring the
combination of the multi-scale atomistic-to-macrospin approximation with the (mechanical)
Brownian dynamics (rotation, displacement), which were traditionally considered separate areas
of knowledge.